17-48529645-G-T

Variant names:

• chr17-48529645-G-T
• rs749227419
• NM_002144.4:c.808C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002144.4(HOXB1):​c.808C>A​(p.Pro270Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOXB1 NM_002144.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919

Genes affected

HOXB1 (HGNC:5111): (homeobox B1) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXB genes located in a cluster on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049764693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB1	NM_002144.4	c.808C>A	p.Pro270Thr	missense_variant	Exon 2 of 2	ENST00000239174.7	NP_002135.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB1	ENST00000239174.7	c.808C>A	p.Pro270Thr	missense_variant	Exon 2 of 2	1	NM_002144.4	ENSP00000355140.5
HOXB1	ENST00000577092	c.*561C>A		3_prime_UTR_variant	Exon 1 of 1			ENSP00000459066.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456640 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723586

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.74
DEOGEN2	Benign	0.095	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.51	.;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.17	N;.
REVEL	Benign	0.10
Sift	Benign	0.37	T;.
Sift4G	Benign	0.81	T;.
Polyphen		0.0030	B;B
Vest4		0.051
MutPred		0.17		Gain of phosphorylation at P270 (P = 0.0067);Gain of phosphorylation at P270 (P = 0.0067);
MVP		0.88
MPC		0.47
ClinPred		0.062	T
GERP RS		0.70
Varity_R		0.037
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs749227419; hg19: chr17-46607007;